This research aims to define the sequence of regression of atherosclerotic plaques by studying serial changes in morphology, chemical composition and peripheral pulsations. It will examine the hypotheses that regressive changes may occur asynchronously and that unstable components may be present in more advanced stages. It will also seek more optimal methods of inducing regression. Its specific aims are: 1) to define sequential morphological, biochemical and functional characteristics of plaques during regression, as well as determine changes in collagen/elastin composition and turnover at plaques sites; 2) and assess variations in plaque susceptibilty to regression based on site, stage, and complications, and to evaluate the effects of combined therapy to lower serum lipids and to influence platelet arterial wall interaction. To accomplish these aims, techniques developed in these laboratories for direct sequential observation and sampling of plaques during progression will be applied to regression. The use of existing colonies of monkeys and dogs with established lesions and the use of animals whose collagen and elastin have been made chronically radioactive will permit determinations of turnover in new and old collagen and elastin. The collagen in plaques will be studied to see if Type I collagen (less crosslinked) remains in plaques as an unstable component. This research promises to investigate the particular problem of regression of more advanced fibrous plaques. Ultimately, this information can be extended to the treatment of patients with established atherosclerosis.